ACTH

What is being tested?
This test measures the level of the hormone ACTH in the blood. ACTH is a hormone produced by the pituitary gland, a gland located in the brain, in the centre of the skull. It is part of the endocrine system, a group of glands that produce hormones acting on organs, tissues and other glands, which helps keep the body in balance. The pituitary produces ACTH and releases it to stimulate the production of cortisol by the adrenal glands (small organs located above the kidneys). Cortisol is important in regulating the metabolism of glucose, proteins and fats, in suppressing the immune system and in maintaining blood pressure. Generally ACTH rises when cortisol is low and falls when it is high.

Patients who do not produce enough cortisol may have symptoms such as muscle weakness, fatigue, weight loss, skin pigmentation (even in areas not exposed to the sun) and loss of appetite. These symptoms are often accompanied by signs such as low blood pressure, low glucose, low sodium and high potassium and calcium levels.

Symptoms suggestive of hypopituitarism include loss of appetite, tiredness, irregular periods, hypogonadism (low levels of male sex hormones), reduced libido, frequent urination at night and weight loss. When the condition is due to a pituitary tumour (usually benign), the patient may also have symptoms caused by pressure on nearby cells and nerves. The tumour may press on the nerves that control vision, causing symptoms such as “tunnel” vision (inability to see objects outside the line of sight), loss of vision in certain areas or double vision, and may also cause recurrent headaches.

What does the result mean?
Changes in ACTH and cortisol are often assessed at the same time.
A rise in ACTH may mean that the patient has Cushing’s disease, Addison’s disease or an ectopic ACTH-secreting tumour. A fall in ACTH may be due to an adrenal tumour, corticosteroid treatment or hypopituitarism.

In some cases interpreting the results can be complex. ACTH and cortisol levels vary during the day. ACTH is generally highest in the morning and lowest at night. It stimulates cortisol production, which rises after ACTH has risen and falls to its lowest level late at night. Diseases that alter ACTH and cortisol production also alter this daily cycle.

Is there anything else I should know?
Assessing changes in cortisol in response to certain medicines helps clarify the picture and reach the right diagnosis. The most commonly used medicine is “Cortrosyn” (cosyntropin, a pharmaceutical form of ACTH) for an ACTH stimulation test, or dexamethasone for a suppression test.

• cosyntropin, like ACTH, stimulates the adrenal glands to produce cortisol. If cortisol levels do not rise after it is given, this means that the adrenal glands are underactive, as in Addison’s disease or hypopituitarism.
• dexamethasone is a very potent medicine that works like cortisol. In healthy people it blocks ACTH production. Testing the response to different doses of dexamethasone makes it possible to assess whether the patient has Cushing’s syndrome and to determine its causes.

Several other medicines may be used, such as insulin, corticotropin-releasing hormone and metyrapone.

Some medicines can raise ACTH, including insulin, amphetamines, levodopa, metoclopramide and RU 486.

Medicines that lower ACTH levels are dexamethasone and other medicines that act like cortisol (including prednisone, hydrocortisone, prednisolone and methylprednisolone) and megestrol acetate.
ACTH secretion can be increased by stress.

ACTH has been used as a medicine in the treatment of multiple sclerosis

1. What is the difference between Cushing’s disease and Cushing’s syndrome?
Cushing’s disease is overstimulation of the adrenal glands by ACTH produced by a (usually benign) tumour of the pituitary. Cushing’s syndrome refers to the same symptoms, but the causes can be different. It can be caused by taking steroid hormones (often used to treat cancer and autoimmune diseases), by tumours of the adrenal glands and by non-pituitary tumours that produce ACTH (usually in the lung).

2. What is Addison’s disease?
It is the name used for primary adrenocortical insufficiency, which occurs when the adrenal cortex is damaged or destroyed and cortisol and other adrenal steroids, including aldosterone, are lacking.

3. My doctor told me that my excess ACTH is not produced in the pituitary. What does this mean?
This is called ectopic ACTH production. It means that ACTH is produced by a tumour located somewhere in the body, often (but not always) in the lungs. This causes Cushing’s syndrome and may lead your doctor to look for the tumour.